Pulmonary involvement in inflammatory bowel diseases: report of a national cohort over the past 5 years

doi:10.21203/rs.3.rs-4644286/v1

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Research Article

Pulmonary involvement in inflammatory bowel diseases: report of a national cohort over the past 5 years

https://doi.org/10.21203/rs.3.rs-4644286/v1

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Background

Chronic inflammatory bowel disease (IBD) is a common illness, with a number of cases constantly rising. Pulmonary involvement is rarely described in children with IBD. This national survey aims to describe the clinical, biological and therapeutic data of IBD children with pulmonary involvement followed from January 2017 to April 2023 in a rare respiratory diseases centre.

Methods

This was a retrospective, observational, descriptive, multicentre study conducted within the French RespiRare network. Socio-demographic characteristics, previous events, clinical and paraclinical data, treatment and evolution were collected via an anonymous secure questionnaire.

Results

Seven IBD children with pulmonary involvement were reported (sex ratio 0.75, median age 10 years, 4 with Crohn disease and 3 with ulcerative colitis). For 2 patients, the discovery of pulmonary involvement was concomitant with the diagnosis of Crohn's disease. Pulmonary symptoms were non-specific or absent. Chest computed tomography scans revealed condensation (n = 5), mosaic appearance (n = 2), excavated (n = 2) or non-excavated (n = 3) nodules or micronodules. Bronchoalveolar lavage revealed hypercellularity with hyperlymphocytosis in 4 patients among 6. Biopsies (n = 5) showed inflammation or granulomas. Organized pneumonia was diagnosed in 5 patients, granulomatosis in 1 and necrotizing pneumonia in 1. Most patients were treated with oral corticosteroids, with a favourable outcome.

Conclusions

This is the first national reported cohort of IBD children with pulmonary involvement. They are discussed in regard to the 29 previous published cases we found in the same period.

Inflammatory bowel disease

extra-digestive manifestation

pulmonary involvement

pediatric

Inflammatory bowel disease (IBD) is a common illness, and the number of cases has been rising steadily for several years, with over 200,000 patients affected and 15,000 new cases each year in France. These diseases can occur at any age, but mainly in young adults. However, around 3% of new diagnoses are made before the age of 18 (IBD in France – Observatoire National des Maladies Inflammatoires Chroniques de l’Intestin). The prevalence of extra-intestinal manifestations is difficult to know precisely, and varies in the literature from 6 to 47%, depending on diagnostic criteria and clinical or sub-clinical nature. They appear to be more frequent in younger patients. These manifestations are important to identify, as they may be present even before the initial diagnosis of IBD [1, 2]. Pulmonary involvement is rare, affecting between 3% and 10% of IBD patients [3, 4], depending on the inclusion criteria and characterization of pulmonary involvement. It can involve the entire tracheobroncho-pulmonary tract and can therefore take many different forms. Lung inflammation (with or without non-caseating granulomas) can be identified in the mucosa of the respiratory tract and the lung parenchyma. Pulmonary involvement appears to be more frequent in ulcerative colitis than in Crohn's disease [1, 2]. The European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) does not recommend regular screening for respiratory disease in children with IBD [5]. A review of the literature reports a few clinical cases of pediatric patient with descriptions of the clinical, paraclinical examinations and proposed treatment [6–26]. However, due to the small number of patients reported, there are no data on the incidence or prevalence of these respiratory disorders in the pediatric population, and no consensus on their management.

The aim of our study was to collect national case reports of children with IBD associated with respiratory disease over the last 5 years from hospital centres for rare respiratory diseases in children. The main objective was to describe the clinical, biological and therapeutic data of children being followed for IBD with pulmonary involvement in France.

Population concerned

The study population included children under 18 years of age over a 5-year period (from 01/01/2017 to 03/04/2023) for whom respiratory involvement in connection with chronic inflammatory bowel disease was diagnosed in a national centre for rare respiratory diseases of children (RespiRare network). We excluded cases of drug hypersensitivity pneumonitis.

Data collection

This was a retrospective, observational, descriptive and multicentre study. For data collection, we used a secure questionnaire to be completed by the doctors responsible for the children. Data were collected anonymously. The questionnaire collected socio-demographic data such as sex and date of birth, place of treatment, and personal and family medical and surgical history. We then collected clinical data, i.e. the initial diagnosis with date and initial symptomatology, as well as more specifically pulmonary and digestive symptomatology, and whether other conditions were present. We also noted the time between onset of pulmonary and digestive symptoms. The results of the various examinations used to establish the diagnosis, the treatment used and the evolution under treatment were noted. The questionnaire was sent to the referring physicians within the French RespiRare network (national network for rare lung diseases). Data were then entered into an anonymized database (Word file).

Data analysis method

The analysis consisted of a descriptive analysis of the results obtained. Numerical frequencies were determined for all the criteria evaluated. Qualitative variables were presented as proportions and numbers, while quantitative variables were expressed as mean and standard deviation.

Ethical aspects

In accordance with French Public Health Law no. 2004 − 806 of August 9, 2004, and its implementing decree, an opinion was sought from the Ethics Committee of the French Pediatric Society. A favourable opinion was issued under n° CERSFP_2022_146-2. Similarly, a request for authorization for health research was filed with the CNIL under file number 923097. Children and their families, and adult patients, were informed by means of a non-opposition form sent by post or delivered personally to the patient and family.

Our French pediatric cohort reported 7 cases of IBD-associated lung disease in the last 5 years (Table 1). The population was composed with 4 girls and 3 boys. Crohn's disease was slightly more common than ulcerative colitis. The average age at IBD diagnosis for our cohort was 10 years (IQR: 3 to 15 years).

Table 1

French cohort of 7 pediatric cases of pulmonary involvement in IBD respected within a 5-year period (January 2017 to April 2023).
Patient number	Age at IBD diagnosis	Gender	Type of IBD	Delay between digestive and pulmonary involvement	Paraclinical	Biopsy	Diagnosis of lung damage	Treatments for lung damage	Evolution
1	11 years old	M	Crohn	Concomitant diagnosis	- CT: diffuse mosaic pattern, alveolar bronchiolar abnormalities of the 2 lower lobes with a more organized condensation focus poster basally on the LLL - BAL: 190 elements/mm³, lymphocytes 50%, macrophages 32%.	Trans-bronchial biopsy: haemorrhagic and fibrinous alveolitis. Absence of fibrosis	Organized pneumonia	Corticosteroids PO 1 mg/kg/d Inhaled corticosteroids/ LABA combination	Mosaic / Restrictive syndrome with diffusion disorder
2	3 years old	M	Crohn	Concomitant diagnosis	- CT: mediastinal adenomegalies, mosaic pattern, diffuse bronchial syndrome, a few submillimetre calcified micronodules and sparse micro nodularity - BAL: 250 elements/mm³, macrophages 60%, lymphocytes 35%.	Bronchial step biopsies: subacute and chronic inflammatory lesions with no specificity	Granulomatosis	Inhaled corticosteroids	Stable
3	13 years old	M	Crohn	1 month	- CT: Bronchial syndrome and multiple branching micronodules of the apical and dorsal segments of the RUL with some confluences in parenchymal focus. - BAL: 56% macrophages, 41% lymphocytes	Lung biopsy: epithelioid and gigantocellular granulomas with necrosis of the right lung	Organized necrotizing pneumonia	Corticosteroids PO	NS
4	6 years old	F	UC	3 years	- CT: apical excavated nodule of the RUL and multiple foci of bilateral plurifocal alveolar condensation of rounded shape or in patches predominating at the level of the basal pyramids and in the periphery - BAL: cells 130 elements/mm³, macrophages 78%, lymphocytes 15%.	Lung biopsy: sparse polymorphonuclear cells and red blood cells, absence of epithelial cells, thin basement membrane, chorion, loose fibrous connective tissue with no significant inflammatory infiltrate.	Organized pneumonia	Antibiotic therapy	Good progress
5	15 years old	F	UC	8 months	- PET scan: dense, subpleural, multifocal pulmonary condensation with aerated bronchogram, mainly involving the apical and posterior superior regions of the 2 lungs. - CT: peripheral condensation with aerotic bronchogram, apexes and upper lobe posterolaterally. Some peripheral or juxta bronchovascular condensations. - BAL: 430 elements/mm³, macrophages 70%, lymphocytes 12%.	Not made	Organized pneumonia	Corticosteroids PO 1mg/kg/d then decrease	Good progress, standardization of CT
6	12 years old	F	UC	9 months	- CT: lung parenchymal condensation of RLL and excavation suggestive of necrotizing pneumonia. - BAL: polymorphic liquid, formula not feasible	Not made	Necrotizing pneumonia	Corticosteroids PO 1 mg/kg/d then decrease Antibiotic therapy	Partial regression Always asymptomatic
7	11 years old	F	Crohn	7 years	- CT: Atypical nodular formations - BAL: 90 elements/mm³, predominantly lymphocytes	Lung biopsy: Organized pneumonia with incipient granulomas	Organized pneumonia	Corticosteroids PO 0.3 mg/kg/d	Regression
BAL: bronchoalveolar lavage PO: per os
CT: computed tomography RLL: right lower lobe
LABA: long-acting bronchodilator RUL: right upper lobe
LLL: left lower lobe UC: ulcerative colitis
NS: not specified

Pulmonary involvement appeared early in the course of the disease. For 2 patients (patients 1 and 2), the discovery of pulmonary involvement was concomitant with the diagnosis of Crohn's disease. They suffered from abdominal pain and diarrhoea, associated with dyspnea and an altered general condition. Patient 1 had also been suffering from fever for several months. Patient 2, with wheezing and cough, was being treated for asthma. For the other 5 patients, the diagnosis of IBD was known before the onset of pulmonary involvement. However, for 3 of them, pulmonary involvement appeared within the first year of the disease. The longest delay between IBD diagnosis and onset of lung involvement was 7 years (IQR: 1 month to 7 years).

Respiratory and extra-respiratory symptoms are resumed in Table 2. For more than half patients, digestive symptoms were typical of IBD, with altered general condition, abdominal pain and diarrhoea. Some also presented with rectal discharge, anaemia or fever. Respiratory signs were non-specific. Symptoms included dyspnea, cough and/or chest pain. Auscultation could reveal wheezing but could be normal as well. The disease could also be completely asymptomatic. Patient 6's lung involvement was discovered incidentally during a digestive computed tomography (CT) performed as part of a pre-therapeutic work-up, with lung sections on the bases. For patient 5, lung involvement was discovered during a PET scan for a prolonged fever, with no other associated symptoms. Only 2 patients suffered from other disorders such as pancreatitis and arthralgia.

Table 2

Respiratory and extra-respiratory symptoms in IBD patients.
Symptoms	Number of patients reached out of 7
Respiratory
Dyspnea	4
Cough	3
Normal auscultation	2
Chest pain	2
Wheezing	1
Extra-respiratory
Altered general condition	5
Abdominal pain	5
Diarrhoea	5
Anaemia	3
Rectorragia	2
Fever	2
Pancreatitis	1
Joint pain	1

All patients benefited from a chest CT to assess lung involvement. Most patients (5 out of 7) had condensation foci (Fig. 1A). More than half showed nodules or micronodules on the CT. Among them, 2 were excavated (Fig. 2). In 2 patients, diffuse bronchiolar involvement was present with a mosaic appearance (Fig. 1B). A PET scan was performed on 1 patient and also revealed pulmonary condensation. Among the 6 patients old enough to have functional pulmonary testing, only 3 patients performed them: 2 had restrictive ventilatory disorders and the 3rd mixed ventilatory disorders. In order to characterize this condition, bronchial endoscopy with bronchoalveolar lavage was performed on all patients. The macroscopic appearance of the bronchial fibreoptic endoscopy was normal. Hypercellularity with hyperlymphocytosis was found in bronchoalveolar lavage in 4 out of 6 patients with interpretable results (IQR 190 to 430 elements/mm³). Biopsies were performed in 5 patients (3 lung biopsies, 1 staged bronchial biopsy at endoscopy and 1 trans-bronchial biopsy). Staged bronchial biopsy and trans-bronchial biopsy were performed in patients with a mosaic appearance on their CT. Pathological analysis revealed subacute and chronic inflammation and alveolitis, respectively. Lung biopsies were performed in patients with micronodules and nodules. Two of the 3 lung biopsies revealed granulomas, one of which was epithelioid and gigantocellular with caseous necrosis. The 3rd lung biopsy was non-contributory.

Based on clinical and paraclinical findings, and in some cases pathological analysis, 5 patients were diagnosed as having organized pneumonia. Among them, 1 was necrotizing. One was a granulomatosis and one a necrotizing pneumonia. There was no difference in involvement according to IBD type.

Most patients were treated with oral corticosteroids. In the case of organized pneumonia, 4 patients were treated with oral corticosteroids and 1 with antibiotics alone. For the patient with a mixed ventilatory disorder, a combination of inhaled corticosteroids (ICS) and long-acting bronchodilators was also used with oral corticosteroids. For granulomatosis, ICS were prescribed. Finally, necrotizing pneumonia was treated with antibiotics combined with oral corticosteroids. Progression was fairly heterogeneous. For more than half the patients, treatment led to regression or even normalization of the CT images. However, for 2 patients, treatment merely stabilized the condition, with symptomatology persisting.

As far as we know, our study is the only one describing a French national cohort of pediatric cases with pulmonary involvement in IBD.

In the literature over the past 20 years, we have identified only 29 pediatric cases of IBD with pulmonary involvement [6–26], involving 19 girls and 10 boys, 23 with Crohn disease and 6 with ulcerative colitis. The average age at diagnosis of pulmonary involvement was 12.4 years old, slightly older than in our study. However, the average age in our study was the age at diagnosis of IBD. The incidence of lung involvement is probably underestimated as there is no study proposing a systematic CT in children with IBD. The clinical manifestations, thoracic radiological features and histology of these 29 cases are summarized in Table 3. For more than half patients, the diagnosis of IBD was unknown at the time of discovery of pulmonary involvement. This confirms, as in our cohort, that lung involvement occurs relatively early in the course of IBD. These cases presented the same non-specific pulmonary symptomatology as our patients. As a result, several patients were initially treated with antibiotics to rule out an infectious cause.

Table 3

Literature review of 18 pediatric cases of lung involvement in IBD.
Articles	Features	IBD type	Initial pulmonary symptoms	Paraclinical	Anatomopathology	Previous IBD treatment	Treatments for lung damage	Evolution
Al-Binali [6]	Boy 11 years old	Crohn's disease Concurrent diagnosis	Pneumonia Cough Exertional dyspnea Base crackling	- CT: nodules without interstitial involvement - PFTs: RVD - BAL: hypercellular, 15% lymphocytes, 80% macrophages	Lung biopsy: granuloma without caseous necrosis	/	No treatment	Spontaneous remission
Ahmed [7]	Girl 9 years old	Crohn's disease Concurrent diagnosis	Dyspnea Stridor	- Bronchial fiberoptic endoscopy: diffuse hemorrhagic tracheitis, progressive edema	Tracheal biopsy: granulomatous disease	/	NS	Improvement
Silbermintz [8]	Girl 13 years old	Crohn's disease previously followed	Cough Back pain Pneumonia	- CT: bilateral nodules and pleural lesions - Normal PFTs then restrictive ventilatory disorder	Lung biopsy: multiple noncaseating epithelial granulomas	Methotrexate, Corticosteroids 6-MP	Infliximab	Remission
Krishnan [9]	Girl 13 years old	Crohn's disease previously followed	Cough Back pain Fever Pneumonia	- CT: multiple pleural and intraparenchymal infiltrates	Lung biopsy: giant cell granulomas without caseous necrosis	6-MP Corticosteroids	Corticosteroids (increased dosage) Infliximab	Remission
Krishnan [9]	Girl 14 years old	Crohn's disease previously followed	Chest tightness Cough Dyspnea	- CT: multiple granulomatous lesions	Lung biopsy: epithelioid giant cell granulomas without caseous necrosis	Mesalazine	Infliximab	Improvement
Krishnan [9]	Boy 17 years old	Crohn's disease previously followed	Chest pain Fever	- CR: bilateral basal infiltrates and bilateral pleural effusions	Lung biopsy: obliterative bronchiolitis and organized pneumonia	Mesalazine 6-MP	Infliximab	Remission
Mahgoub [10]	Boy 5 years old	Crohn's disease previously followed	Cough Dyspnea	- CR: extensive airspace shadowing and several ring shadows - CT: changes consistent with interstitial lung disease	Lung biopsy: noncaseating epithelioid granulomatous inflammation, lymphocytic interstitial pneumonitis and focal scarring	Sulfasalazine Corticosteroids	Corticosteroids Azathioprine	Stability
Carvalho [11]	Girl 13 years old	UC previously followed	Abdominal pain Diarrhoea Fever Night sweats	- CT: nodules - PFTs: OVD	Lung biopsy: alveolar inflammation	/	Corticosteroids Mésalazine 6-MP Antibiotic	Remisson
Levenbrown [10]	Girl 15 years old	Crohn's disease Concurrent diagnosis	Dry cough 3 pneumonias in 6 months Decreased bilateral vesicular murmur	- CT: peribronchovascular nodules, infiltration, mediastinal lymphadenopathy - PFTs: RVD - BAL: normal	Lung biopsy: acute and chronic non-caseous granulomatous inflammation ± necrosis, cryptogenic organized pneumonia	/	Corticosteroids Methotrexate Mesalazine	Slight improvement
Roblin [11]	Girl 13 years old	Crohn's disease Concurrent diagnosis	Dyspnea Cough Fever	- CT: 2 excavated lesions - BAL: macrophages	Lung biopsy: ulceration of bronchial mucosa with necrotic inflammatory remodelling	/	Corticosteroids Azathioprine	Improvement
Basseri [14]	Boy 17 years old	UC previously followed	Unilateral chest pain Shortness of breath Fever	- CR: Multiple bilateral patchy nodular opacities - CT: Multiple bilateral nodules of varying sizes	Lung biopsy: Multifocal acute alveolitis with multiple abscesses	Mesalazine Corticosteroids	Corticosteroids	Improvement
Gut [15]	Girl 15 years old	UC previously followed	Productive cough, wheezing	- CR: Mild bilateral hyperinflammation, bronchial thickening - CT: Diffuse bronchiectasis of all lung fields	Not performed	NS	Antibiotic Corticosteroids	Improvement
Pain-Prado [12]	Girl 8 years old	Crohn's disease Concurrent diagnosis	Fever Tachypnea	- CT: multiple disseminated irregular stellate nodules - BAL: cellularity 450000 elements/mm3, 26% lymphocytes - PFTs: normal	Not performed	/	No treatment	Remission
Navaneethan [13]	Girl 11 years old	Crohn's disease Concurrent diagnosis	Cough Decreased left base vesicular murmur	- CR: left condensation and pleural effusion - BAL: cellularity 2719 elements/mm³, 93% PNN, 3% lymphocytes, 2% macrophages	Not performed	/	Corticosteroids Infliximab	Remission
Navaneethan [13]	Girl 17 years old	Crohn's disease previously followed	Cough Dyspnea Fever Bilateral crackles Skin lesions	- CT: excavated lesions - BAL: numerous macrophages and neutrophils	Not performed	Azathioprine	Infliximab	Improvement
Chiaro [14]	Girl 14 years old	Crohn's disease previously followed	Fever Cough Dyspnea Whistling Chest pain	- CT: multiple pulmonary nodules with parenchymal infiltrates and diffuse bilateral interstitial inflammation - BAL : normal	Lung biopsy: non-caseating granulomatous inflammation with multinucleated giant cells	Mesalazine Corticosteroids 6-MP Methotrexate Infliximab Adalimumab	Corticosteroids	Improvement
Nelson [15]	Girl 9 years old	Crohn's disease previously followed	Cough Dyspnea Chest pain	- CT: multiple pulmonary nodules - PFTs: restrictive ventilatory disorder	Lung biopsy: necrotizing granuloma	NS	Corticosteroids Infliximab Azathioprine	Remission
Darby [16]	Boy 11 years old	Crohn's disease Concurrent diagnosis	Cough	- CT: focus of condensation, ground glass nodules	Not performed	/	Infliximab	Remission
Thaver [17]	Girl 5 years	Crohn's disease Concurrent diagnosis	Asymptomatic	- CT: multiple pulmonary nodules, pleural effusion - BAL: few bronchial cells and scattered macrophages	Lung biopsy: necrotizing granulomas with fibrosis and chronic inflammation	/	Mesalazine Infliximab Methotrexate	Stability
Ongun [18]	Boy 5 years	Crohn's disease Concurrent diagnosis	Asymptomatic Post-operative ARDS	- CT: condensation with bronchiectasis and ground-glass areas	Not performed	Infliximab	Corticosteroids	Improvement
Inoue [19]	Boy 14 years old	Crohn's disease previously followed	Dyspnea Fever Chest pain	- CT: infiltration, atelectasis and pleural effusion, cavern	- Puncture: exudate, negative cultures - Lung biopsy: fibrosis and infiltration of inflammatory cells in the form of organized pneumonia	Mesalazine Salazopyrine	Corticosteroids	Improvement
Russi [24]	Girl 17 years old	UC previously followed	Chronic purulent cough	- CR: Normal - CT: “Tree-in-but” opacities, mild bronchiectasis, bronchial wall thickening - BAL: purulent bronchitis, 99% neutrophils - PFTs: moderate OVD	Not performed	Infliximab	Corticosteroids	Improvement
Taylor [25]	Boy 16 years old	UC previously followed	Pleuritic chest pain Fever	- CR: right upper and left lower lobe pulmonary opacities - CT: multiple pulmonary nodules with associated hilar lymphadenopathy	Lung biopsy n°1: necrotic neutrophilic nodules without granulomas Lung Biopsy n°2: cryptogenic organizing pneumonia	Azathioprine	Corticosteroids Mesalazine Azathioprine Infliximab	Multiple recurrences
Taylor [25]	Girl 10 years old	Crohn's disease previously followed	Asymptomatic	- CT: multiple small bilateral pulmonary nodules	Lung biopsy: non-necrotizing granulomatous bronchiolitis	Adalimumab	Dose increase adalimumab
Taylor [25]	Girl 17 years old	Crohn's disease Concurrent diagnosis	Asymptomatic	- CT: extensive tree-in-bud opacities predominantly in the bilateral lower lobes of the lung	Lung biopsy: necrotizing granulomatous inflammation and focal organizing pneumonia	/	No treatment	Improvement
Taylor [25]	Boy 14 years old	Crohn's disease previously followed	Cough	- CT: diffuse pulmonary micronodules	Lung biopsy: granulomatous inflammation	Corticosteroids	Infliximab Methotrexate Corticosteroids	Improvement
Taylor [25]	Girl 14 years old	Crohn's disease previously followed	Pleuritic chest pain Cough	- CR: right upper lobe nodule - CT: bilateral pulmonary nodules, some of which demonstrate central cavitation	Lung biopsy: chronic interstitial pneumonitis with minimal patchy organizing pneumonia	Infliximab Adalimumab Vedolizumab	No treatment	Improvement
Taylor [25]	Girl 13 years old	UC previously followed	Chronic, productive cough Dyspnea	- CR et CT: multiple pulmonary nodules - PFTS: reversible OVD	Lung biopsy: fibroinflammatory process favouring cryptogenic organizing pneumonia	No treatment	Albuterol Fluticasone inhaler	Improvement
Cao [20]	Boy 11 years old	Crohn's disease Concurrent diagnosis	Asymptomatic	- CT: pulmonary nodules - PFTs: RVD	Lung biopsy: granulomatous lesions without caseous necrosis	/	Corticosteroids Azathioprine	Improvement
BAL: bronchoalveolar lavage PO: per os
CR: chest x-ray PFTs: pulmonary function test
CT: thoracic computed tomography RVD: restrictive ventilatory disorder
IV: intravenous OVD: obstructive ventilatory disorder
NS: not specified 6-MP: 6-mercaptopurinol

Lung imaging would be abnormal in 37–53% of IBD cases, whereas patients are symptomatic in around 10% of cases [27]. The radiological expression of lung involvement in some cases was similar to that in our study: nodules, infiltrates and condensation. However, a greater number of cases also revealed other types of involvement, such as bronchiectasis, pleural effusion and tracheal involvement. Bronchial endoscopy and bronchoalveolar lavage were of limited value, unlike our cohort, where we were able to demonstrate the presence of hypercellularity with hyperlymphocytosis in lung involvement. Up to 90% of patients with active intestinal disease present with abnormal respiratory function testing, most often a restrictive ventilatory disorder [27]. A recent study assessing respiratory function in children with inflammatory bowel disease found abnormal EFR in 26% of patients, obstructive ventilatory disease in 14% and restrictive ventilatory disease in 8%. None of the patients with abnormal tests presented any symptoms from the respiratory tract. The pulmonary function abnormalities did not depend on either disease activity or on immunosuppressive therapy [28]. In our cohort, we found only restrictive ventilatory disorders. However, a larger number of patients in the literature also showed obstructive ventilatory disorders in just under half the cases. From an anatomopathological point of view, literature reported a large number of granulomatosis (15 patients), as well as organized pneumonia (6 patients) and bronchiolitis obliterans. In 2 patients, the disease progressed to fibrosis.

Therapeutic management seems to have evolved over time. A case report published in 2015 raises the possibility of using infliximab, belonging to the anti-TNFα class, to treat pulmonary involvement in IBD [29]. Indeed, infliximab has been shown to be effective in other extra-digestive manifestations after failure of immunosuppressive treatments, such as spondyloarthropathies, refractory erythema nodosum, pyoderma gangrenosum and uveitis [29]. Thus, for 5 of the 29 published cases, treatment consisted solely of courses of anti-TNFα, whether or not the diagnosis of Crohn's disease was previously known [8, 9, 17, 20]. Five other patients were treated with a corticosteroid/infliximab combination with or without other associated treatments [9, 17, 19, 25]. However, there are no studies demonstrating the efficacy of this treatment in pulmonary disease. In the case reported by Ongun et al [22], pulmonary involvement developed despite infliximab and treatment had to be changed to corticosteroids. Five other case reports have since been published using only corticosteroids as treatment [14, 18, 22–24] and six in combination with another systemic treatment [10–13, 15, 26].

Despite growing awareness and knowledge of IBD-associated lung disease, little is known about its treatment. Current treatment recommendations are empirical and based on expert opinion, secondary to case reports on the use of inhaled or systemic corticosteroids, as well as by analogy with certain lung diseases closely related to this condition, such as certain diffuse interstitial lung diseases or sarcoidosis [29, 30]. Under treatment, and it would appear regardless of the therapy used, improvement or even complete remission is usually observed. However, the disease may persist and progress to fibrosis in some cases. No documentation is available on the long-term evolution of pulmonary damage. Only one of the above cases had relapsed at the time of writing [25]. However, the follow-up period remains short, and no paraclinical data have been reported.

At all, with our series, only 36 cases of respiratory involvement appear to have been described in pediatric patients with IBD. Pulmonary involvement therefore appears to be rarer than previously reported [3, 4]. However, we note a probable selection bias, with cases collected only from pediatric pulmonologists in rare disease reference centres. These are therefore probably the most severe cases, with less severe cases possibly going unreported. With little or no specific symptomatology, and a very low incidence, systematic screening for pulmonary involvement does not seem appropriate in pediatric IBD.

This study describes a cohort of pediatric patients with their clinical manifestations, paraclinical features and treatments used in cases of pulmonary involvement in IBD. Respiratory involvement is rare and probably under-diagnosed. It is often early onset, may precede the diagnosis of IBD, is non-specific, and responds well to corticosteroid treatment.

- Ethics approval This is an observational study. The Comité d’Ethique de la Recherche de la Société Française de Pédiatrie (CERSFP_2022_146-2) and the Commission Nationale de l’Informatique et des Libertés (CNIL 923097) gave their consents.

- The authors state that all the methods applied were in line with the ethical standards defined in the Declaration of Helsinki.

- Consent to participate and publication Patients and represent legal were informed by means of a non-opposition form, and were given the right to access, rectify, delete, oppose, limit and digitally "die" their child's data, in accordance with the European Directive (95/46/EC) and the ethics committee.

- Consent to publication: Written and informed consent to publication has been obtained via the no-objection form.

- Use of any animal or human data or tissue: not applicable

Competing interests

The authors declare that they have no competing interests.

Funding

No funding

Author contribution

LP collected the data, were in charge of the data monitoring, reviewed and approved the manuscript.

ACKNOWLEDGMENTS

The authors would like to thank the patients who contributed towards this study.

Availability of data and materials

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

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Pulmonary involvement in inflammatory bowel diseases: report of a national cohort over the past 5 years

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Introduction

Materials and methods

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Data collection

Data analysis method

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Results

Discussion

Conclusion

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